A multidisciplinary approach will be employed to investigate the fundamental biochemical, biophysical and neurophysiological processes involved in the neural regulation of normal salivary function. Two complimentary salivary gland preparations will be exploited in this collaborative investigation: the neuro-salivary gland system of the aquatic snail Helisoma and the major salivary glands of the laboratory mouse. The simpler invertebrate gland preparation will serve as a model system in which new conceptual and methodological approaches will be developed and tested. Experience and insights derived from this model system will then be applied to the study of the more complex mammalian gland preparation. First, we will analyze membrane currents that underlie the action potential in snail salivary glands using a single sucrose gap voltage-clamp technique. We will determine the extent to which the early inward current is carried by external Na ion and Ca2 ion. We will also attempt to voltage-clamp mouse parotid glands in order to analyze the ionic basis of ACh induced secretory potentials. Second, we will utilize vital dyes that change their optical properties (absorbance and/or fluorescence) in a linear fashion with intracellular membrane potential, to monitor electrical activity in an extended region of the gland. The spatial/temporal spread of excitation in glands stained with such potentiometric probes will be resolved using a 15-channel photodiode array. These data will be correlated with light and electron microscopic studies of the regional distribution of excitatory synaptic terminals within the gland. Third, we will correlate secretory potentials in acinar gland cells with changes in their level of intracellular metabolism, their release of Ca2 ion and alterations in salivary pH levels. This will be accomplished using multi-wavelength spectroscopy to simultaneously measure the membrane potential, redox states of pyridine nucleotides and flavoproteins, Ca2 ion efflux and pH values.